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Key Event: 1263

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Necrosis

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Necrosis

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Tissue

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
necrotic cell death		increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
AOP on basal cytotoxicity	AdverseOutcome	Mathieu Vinken (send email)	Open for comment. Do not cite
MPs & Cd induced inflammation-to-cancer transition in liver	KeyEvent	Wei Mu (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
Not Otherwise Specified	Not Specified

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Necrosis is an uncontrolled form of cell death triggered by injury, trauma, or infection^[1]. Its cellular mechanisms involve a cascade of events that break down cellular components and release intracellular contents into the extracellular space^[2]. Unlike non-inflammatory cell death, the released intracellular contents activate the immune system and harm neighboring cells, frequently causing localized inflammation and tissue damage^[3-4].

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

1. Morphological Evaluation: Live-cell phase-contrast microscopy reveals classic necrotic features, such as high-amplitude organelle/cellular swelling ("ballooned" morphology) followed by plasma membrane rupture. Cytospin samples with eosin–methylene blue staining further identify necrotic cells by their "ghost cell" appearance with ruptured cytoplasm and swollen intact nuclei^[5].

2. Membrane Permeability & Caspase Inactivity: Multiparametric flow cytometry using Annexin V-FITC and Propidium Iodide (PI) shows an Annexin V⁺/PI⁺ profile due to rapid plasma membrane disruption. Combining PI with FLICA probes yields a FLICA^-/PI⁺ pattern, confirming the absence of caspase activation^[5].

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

References

List of the literature that was cited for this KE description. More help

[1] Golstein P, Kroemer G. Cell death by necrosis: towards a molecular definition. Trends Biochem Sci. 2007 Jan;32(1):37-43. doi: 10.1016/j.tibs.2006.11.001. Epub 2006 Dec 1. PMID: 17141506.

[2] Khalid N, Azimpouran M. Necrosis Pathology. 2023 Mar 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. PMID: 32491559.

[3] Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P. Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol. 2014 Feb;15(2):135-47. doi: 10.1038/nrm3737. PMID: 24452471.

[4] Park W, Wei S, Kim BS, Kim B, Bae SJ, Chae YC, Ryu D, Ha KT. Diversity and complexity of cell death: a historical review. Exp Mol Med. 2023 Aug;55(8):1573-1594. doi: 10.1038/s12276-023-01078-x. Epub 2023 Aug 23. Erratum in: Exp Mol Med. 2023 Sep;55(9):2083. doi: 10.1038/s12276-023-01107-9. PMID: 37612413; PMCID: PMC10474147.

[5] Costigan A, Hollville E, Martin SJ. Discriminating Between Apoptosis, Necrosis, Necroptosis, and Ferroptosis by Microscopy and Flow Cytometry. Curr Protoc. 2023 Dec;3(12):e951. doi: 10.1002/cpz1.951. PMID: 38112058.